Guoshuang Shen

Associations between interleukin-1 polymorphisms and gastric cancers among three ethnicities

AIM To investigate the associations between interleukin (IL)-1B and IL-1RN polymorphisms and gastric cancers among the Tibet, Hui and Han ethnicities. METHODS Genomic DNA was extracted from peripheral blood of 210, 205, and 202 healthy volunteers and from 155, 158, and 197 gastric cancer patients from the Tibet, Hui, and Han populations, respectively. Polymorphisms in IL-1B and IL-1RN were analyzed by denaturing high-performance liquid chromatography. RESULTS Carriers of the IL-1B-31 CC genotype had an increased risk of intestinal type gastric cancer [odds ratio (OR) = 2.17, P = 0.037] in the Tibet ethnicity. Carriers of the IL-1B 2/L genotype had an increased risk of both intestinal and diffuse types of gastric cancer (OR = 2.08, 2.31, P = 0.007, 0.016, respectively) in the Hui ethnicity. In the Han population, carriers of the IL-1B-31 CC, IL-1B-511CT, TT genotypes had increased risk of intestinal type gastric cancer (OR = 2.51, 2.74, 5.66, P = 0.005, 0.002, 0.000, respectively). CONCLUSION IL-1B and IL-RN genotypes may differentially contribute to gastric cancer among the Tibet, Hui, and Han ethnicities in the Qinghai area of China.

Association of HER2 status with prognosis in gastric cancer patients undergoing R0 resection: A large-scale multicenter study in China

AIM To determine whether the positive status of human epidermal growth receptor 2 (HER2) can be regarded as an effective prognostic factor for patients with gastric cancer (GC) undergoing R0 resection. METHODS A total of 1562 GC patients treated by R0 resection were recruited. HER2 status was evaluated in surgically resected samples of all the patients using immunohistochemical (IHC) staining. Correlations between HER2 status and clinicopathological characteristics were retrospective analyzed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard model, stratified by age, gender, tumor location and tumor-node-metastasis (TNM) stage, with additional adjustment for potential prognostic factors. RESULTS Among 1562 patients, 548 (positive rate = 35.08%, 95%CI: 32.72%-37.45%) were HER2 positive. Positive status of HER2 was significantly correlated with gender (P = 0.004), minority (P < 0.001), tumor location (P = 0.001), pathological grade (P < 0.001), TNM stage (P < 0.001) and adjuvant radiotherapy (74.67% vs 23.53%, P = 0.011). No significant associations were observed between HER2 status and disease free survival (HR = 0.19, 95%CI: 0.96-1.46, P = 0.105) or overall survival (HR = 1.19, 95%CI: 0.96-1.48, P = 0.118) using multivariate analysis, although stratified analyses showed marginally statistically significant associations both in disease free survival and overall survival, especially among patients aged < 60 years or with early TNM stages (I and II). Categorical age, TNM stage, neural invasion, and adjuvant chemotherapy were, as expected, independent prognostic factors for both disease free survival and overall survival. CONCLUSION The positive status of HER2 based on IHC staining was not related to the survival in patients with GC among the Chinese population.

Impact on long-term survival of the number of lymph nodes resected in patients with pT1N0 gastric cancer after R0 resection: A multicenter study in China

Abstract Although studies on the association between the number of lymph nodes resected and prognosis in patients with pT2–4N0 stages of gastric cancer have reported consistent results, there is no consensus on the optimal number of lymph nodes to be examined for pT1N0 stage gastric cancer. The aim of this study was to evaluate the long-term effect of the number of lymph nodes removed on the outcomes of patients with pT1N0 stage gastric cancer after R0 resection. From December 2009 to December 2011, 227 patients undergoing R0 resection of pT1N0 stage gastric cancer at 4 Chinese centers were enrolled in this study. Patients were assigned to 2 groups according to the number of lymph nodes dissected (⩽15 or > 15). Standard survival methods and restricted multivariable Cox regression models were applied. More women (P = 0.031) were in the ⩽15 group than in the >15 group. The mean number of lymph nodes removed from women was greater than that from men (P = 0.007). The 5-year survival rate was significantly higher in the >15 lymph nodes resected group than the ⩽15 group. The number of lymph nodes resected was identified as an independent prognostic factor and was significantly correlated with overall survival (OS). A lymphadenectomy with dissection of more than 15 lymph nodes improved the long-term survival of patients with pT1N0 gastric cancer after R0 resection. Therefore, it is necessary to consider removing more than 15 lymph nodes among such patients.

Cardia and Non-Cardia Gastric Cancer Have Similar Stage-for-Stage Prognoses After R0 Resection: a Large-Scale, Multicenter Study in China

Although the clinicopathological features of cardia gastric cancer (GC) differ from those of non-cardia GC, it is unclear whether the former has poorer prognosis than the latter. The aim of this study was to compare clinicopathological characteristics and prognosis between cardia and non-cardia GC. From December 2009 to December 2011, 1633 patients who had undergone R0 resection of GC at four Chinese centers were enrolled in this study. Their clinicopathological features and survival outcomes were evaluated. Compared with non-cardia GC, cardia GC was associated with a significantly higher proportion of male patients, older age, more advanced pathological stage, and less-favorable clinicopathological features at diagnosis. The 5-year survival rate was significantly lower in the cardia GC group than in the non-cardia GC group. However, no significant difference in overall survival (OS) was observed between the two groups at any pathological TNM stage. Pathological stage was confirmed as an independent prognostic factor of OS. More advanced disease represents most of the cases in this Chinese population. Compared with patients with non-cardia GC, patients with cardia GC were diagnosed at a more advanced stage and had worse prognosis after undergoing R0 resection. However, cardia and non-cardia GCs have similar stage-for-stage prognoses.

Adjuvant chemotherapy with S-1 plus oxaliplatin improves survival of patients with gastric cancer after D2 gastrectomy: A multicenter propensity score-matched study

AIM To investigate the safety and efficacy of S-1 plus oxaliplatin (SOX) as an adjuvant chemotherapy regimen in gastric cancer (GC) after D2 dissection. METHODS GC Patients who underwent D2 gastrectomy from September 2009 to December 2011 in four Chinese institutions were enrolled. Patients with stage IB-IIIC GC, who received adjuvant SOX treatment were matched by propensity scores with those who underwent surgery alone and those who conducted capecitabine plus oxaliplatin (XELOX) regimen. Disease-free survival (DFS) and overall survival (OS) were compared among the groups. In addition, adverse events in SOX patients were analyzed. RESULTS Of 1944 GC patients who underwent D2 dissection, 867 were included for analysis. One hundred and seventeen patients treated with SOX were matched to 234 patients who conducted surgery alone. Fifty-seven patients treated with SOX were matched to 57 patients who received XELOX. The estimated five-year DFS was 57.5% in the adjuvant SOX group which was higher than that (44.6%) in the surgery alone group (P = 0.001); and the estimated five-year OS was 68.3% which was higher than that (45.8%) of surgery alone group (P < 0.001). Survival benefit was also revealed in stage III and > 60 years old subgroups (P < 0.001 and P = 0.015, respectively). Compared with XELOX regimen, SOX showed no significant difference in DFS (P = 0.340) and OS (P = 0.361). The most common ≥ 3 grade adverse events of SOX regimen were neutropenia (22.6%), leukopenia (8.9%) and thrombocytopenia (5.6%). CONCLUSION Compared with surgery alone, SOX regimen significantly improves the long-term survival and has acceptable toxicity in patients with stage IB-IIIC GC after D2 dissection. It may be a novel adjuvant chemotherapy regimen in GC patients.

Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development

Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Compared to the effect of placebo, it improved both progression-free survival (PFS) and overall survival (OS) in a phase III trial in patients with advanced non-small-cell lung cancer (NSCLC), despite progression of the cancer after two lines of prior treatments. Recently, the China Food and Drug Administration (CFDA) approved single agent anlotinib as a third-line treatment for patients with advanced NSCLC. Moreover, a randomized phase IIB trial demonstrated that anlotinib significantly prolonged the median PFS in patients with advanced soft tissue sarcoma (STS). Anlotinib also showed promising efficacy in patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma (mRCC). The tolerability profile of anlotinib is similar to that of other tyrosine kinase inhibitors that target VEGFR and other tyrosine kinase-mediated pathways; however, anlotinib has a significantly lower incidence of grade 3 or higher side effects compared to that of sunitinib. We review the rationale, clinical evidence, and future perspectives of anlotinib for the treatment of multiple cancers.

Novel fluoropyrimidine-based chemotherapy for advanced well-differentiated neuroendocrine tumors: a clinical update

ABSTRACT Introduction: Patients with advanced well-differentiated neuroendocrine tumors (NETs) who have bulky and/or symptomatic and/or rapidly progressive disease require chemotherapy treatment. Areas covered: This review summarizes the accumulating evidence for treatment with fluorouracil-based chemotherapy in well-differentiated NETs. The main clinical studies, toxicity and predictors of fluorouracil- based chemotherapy regimens in well-differentiated NETs are discussed, along with the current issues, future research directions and therapeutic prospects. Expert opinion: Somatostatin analogs may control symptoms of hormone excess and tumor growth in patients with well-differentiated metastatic NETs, and biological therapies may improve progression-free survival for these patients. However, chemotherapy leads to higher objective response rates and symptom control by reducing tumor bulk. The low response rate and significant toxicities of conventional chemotherapy regimens limit their widespread use. Fortunately, some novel fluoropyrimidine-based treatment including fluorouracil, capecitabine, or S-1 based chemotherapy with or without antiangiogenic agents have been investigated in recent years. These treatments showed significant efficacy and less toxicity in pancreatic and non-pancreatic metastatic well-differentiated NETs. Additionally, non-pancreatic well-differentiated NETs have also achieved similar tumor response or survival comparable to pancreatic NETs. Moreover, some predictors of response to these treatment regimens have been evaluated.

Relationship between Topoisomerase II Alpha Overexpression and Prognosis in Chinese Gastric Cancer Patients.

The aim of this study was to investigate topoisomerase II alpha (TOP2α) overexpression and its association with clinicopathological features and prognosis in gastric cancer (GC) patients. All selected GC patients at Affiliated Hospital of Qinghai University and Cancer Hospital, Chinese Academy of Medical Sciences, between December 2009 and December 2011, had formalin-fixed and paraffin-embedded tumor tissues. The patients received a telephone follow-up or in-/outpatient review, and their clinicopathological features and prognoses were analyzed. Also, the relationship between TOP2α expression and postoperative chemotherapy in GC patients was estimated. The results of the study showed that TOP2α overexpression correlated with location of tumor, depth of invasion, and pTNM stage. Moreover, it was associated with lower 5-year overall survival (OS) in noncardia GC patients younger than 60 years, with multivariate analysis demonstrating that it was an independent prognostic factor for these patients. Univariate analysis and multivariate analysis showed that TOP2α overexpression was associated with worse 5-year OS in noncardia GC patients ≤ 60 years receiving postoperative chemotherapy. TOP2α overexpression exhibited associations with location of tumor, depth of invasion, pTNM stage, and postoperative chemotherapy, making it a potential target for early diagnosis of GC patients. In addition, TOP2α overexpression was shown to be a predictor of 5-year OS in both noncardia GC patients ≤ 60 years and noncardia GC patients ≤ 60 years and receiving postoperative chemotherapy.

Is it a protective factor of Helicobacter pylori infection in prognosis of all gastric cancer

Purpose - We aimed to assess whether Helicobacter pylori infection influences prognosis in gastric cancer patients (GC). Methods - We systematically searched MEDLINE, PubMed, EBSCO, EMBASE, and the Cochrane Library (CENTRAL) Register from inception to June 1, 2017. Overall survival (mean OS) or disease-free survival (mean DFS) in GC patients were calculated using the hazard ratio (HR) and 95% confidence intervals (95% CIs). Results - In total, 19 articles with 4,321 GC patients were enrolled. Helicobacter pylori infection is associated with longer OS (HR 0.73; 95% CI 0.60-0.89; P < 0.001) and DFS (HR 0.75; 95% CI 0.53-1.07; P = 0.002) in GC patients overall. For our subgroup analysis, the pooled HRs and 95% CIs were as follows: China (OS: HR 0.95; 95% CI 0.63-1.42; P = 0.804 and DFS: HR 0.88; 95% CI 0.50-1.56; P = 0.658), Europe (OS: HR 0.69; 95% CI 0.52-0.92; P = 0.010 and DFS: HR 0.62; 95% CI 0.32-1.17; P = 0.141), United States (OS: HR 0.77: 95% CI 0.56-1.06; P = 0.105), Korea (OS: HR 0.45; 95% CI 0.27-0.75; P = 0.002 and DFS: HR 0.45; 95% CI 0.24-0.83, P = 0.011), and Turkey (OS: HR 0.94; 95% CI 0.52-1.70; P = 0.839 and DFS: HR 0.95; 95% CI 0.53-1.71, P = 0.864). Moreover, for R0 or M0 patients, H. pylori infection is associated with better OS and DFS (P all values < 0.05). Conclusions - Helicobacter pylori infection has a better prognosis in GC patients from Korea and Europe. Helicobacter pylori infection has no association with prognosis for China, the United States, or Turkey. Also, H. pylori infection has a better prognosis in R0 resection or M0 GC patients.

Impact of High Altitude on Clinicopathological Features and Prognosis after R0 Resection for Gastric Cancer: A Population-Based Multicenter Study

Geographic variation has an important role in both carcinogenesis and prognosis of gastric cancer (GC). High altitude is a special hypoxic environment that is also correlated with the occurrence of GC. Different onset features and prognoses of GC in high altitude with respect to plains are rarely reported and remain unknown. This multicenter study compared different clinicopathological characteristics and prognoses of patients with resected GC who were from locations of both high altitudes and plains in China. From December 2009 to December 2011, patients with resected GC were retrospectively recruited at four centers located at high altitudes and the plains. Clinicopathological data were analyzed to explore the differences between the two groups. The Cox proportional-hazards model was used to investigate the prognostic factors for GC and estimate the independent impact of altitude on long-term survival after adjusting for covariates. Noncardia GC, from a moderate to well tumor grade, was more common in patients from high altitudes. Moreover, a higher proportion of moderate to well and moderate tumor grade and younger age of onset was found in patients with noncardia GC coming from high altitudes. Different overall survival (OS) presented in noncardia GC rather than cardia GC, with 69.94% GC-related 3-yr OS in high altitude versus 75.23% in the plains. High altitude was confirmed as a significant prognostic factor for noncardia GC (the hazard ratio for high altitude vs. plains was 1:50, with a 95% confidence interval; 1.06-1.82, p = 0.018) through a multivariate Cox proportional-hazards model analysis. This prognostic value was independent of all other factors. High altitude has an important role in clinicopathological features and prognosis of GC. Improvements in GC diagnosis and management at high altitudes are urgently needed.